Bacteriological profile and antibiogram of uropathogens isolated from obstetrics and gynaecology patients in a tertiary care hospital

Background: Urinary tract infection (UTI) is a common complication occurring in obstetric patients, posing adverse risks to both the mother and fetus. The aim of this study is to analyse the bacteriological profile and antimicrobial susceptibility pattern of uropathogens in obstetrics and gynaecology ward for the effective treatment. Methods: A total of 404 urine samples from pregnant women with different gestational age were processed for the isolation of uropathogens and tested against ten classes of antibiotics. Uropathogens from significant bacteriuria cases were isolated and identified by standard procedures from January 2020 to December 2021. Antibiotic susceptibility was studied by Kirby Bauer disk diffusion method. Results: Significant bacteriuria in 16.3% samples, Escherichia coli (E. coli) was the most common uropathogens followed by Enterococcus sp. and Klebsiella pneumoniae (K. pneumoniae). E. coli showed highest resistance to ceftazidime, cotrimoxazole and ciprofloxacin while exhibiting high sensitivity to imipenem, meropenem, and amikacin. Moreover, major proportion of isolates of K. pneumoniae were resistant against ceftazidime, ciprofloxacin, and nitrofurantoin; and for Enterococcus species against penicillin and gentamycin, but 100% sensitive to vancomycin and teicoplanin, and 92.3% to linezolid. Conclusions: There is a need for screening of antenatal patients for UTI and it is recommended that pregnant women should undergo periodic screening for UTI, so as to monitor the sensitivity pattern of the uropathogens and for the development of specific antibiotic policies based on local susceptibility patterns.

Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells

Surfactant Protein D (SP-D) is an integral molecule of the innate immunity secreted by the epithelial cells lining the mucosal surfaces. Its C-type lectin domain offers pattern recognition functions while it binds to putative receptors on immune cells to modify cellular functions. Activated PBMCs and increased serum levels of SP-D are observed under a range of pathophysiological conditions including infections. Thus, we speculated if SP-D can modulate systemic immune response via direct interaction with activated PBMCs. Here, we have examined interaction of a recombinant fragment of human SP-D (rhSP-D) on PHA-activated PBMCs. We observed a significant downregulation of TLR2, TLR4, CD11c and CD69 upon rhSP-D treatment. rhSP-D inhibited production of Th1 (TNF-α and IFN-γ) and Th17 (IL-17) cytokines along with IL-6. Interestingly, levels of IL-2, Th2 (IL-4) and regulatory (IL-10 and TGF-β) cytokines were unaltered. Differential expression of co-stimulatory CD28 and co-inhibitory CTLA4 expression along with their ligands CD80 and CD86 revealed selective up-regulation of CTLA4 at both mRNA and protein level. In addition, rhSP-D induced apoptosis only in the activated but not in non-activated PBMCs. Blockade of CTLA4 inhibited rhSP-D mediated apoptosis, confirming an involvement of CTLA4 in induction of apoptosis. We conclude that SP-D restores immune homeostasis: it regulates expression of immunomodulatory receptors and cytokines, which is followed by apoptosis induction of immune-activated cells. These findings appear to suggest a general role for SPD in immune surveillance against activated immune cells

Surfactant protein D in immune surveillance against cancer

Surfactant protein D (SP-D) is an innate immune molecule that was originally discovered in the lungs as a part of pulmonary surfactant system. Later on, it became evident that SP-D has extensive tissue distribution that lent its credentials as a versatile innate immune molecule of mucosal system. In addition to its ability to protect against pathogens and allergens, and to modulate inflammatory reactions, SP-D has emerged as an immune surveillance molecule against cancer. SP-D can induce apoptosis in a variety of cancer cell lines and primary cancer cells derived from patients, including lung, pancreatic, prostate, ovarian and breast cancers. The apoptotic mechanisms including pathways, signaling and key mediators involved, have been delineated. The most striking feature of recent studies is the demonstration that a recombinant form of human SP-D (rfhSP-D) composed of homotrimeric C-type lectin domains can bring about these anti-tumor effects, raising the possibility of a therapeutic development. In addition to apoptosis induction, rfhSP-D can also interfere with epithelial-to-mesenchymal (EMT) transition in pancreatic cancer. In view of the above-mentioned in vitro studies, a recent bioinformatics analysis has examined if SP-D can serve as a potential prognostic marker for human lung cancer. It appears that compared to their normal tissue counterparts, there is a lower expression of SP-D in lung, gastric, and breast cancers, as opposed to ovarian cancer. In the lung cancer, the existence of SP-D is likely to be associated with a favourable prognosis

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution

Abstract The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor